Black mulberry fruit extract alleviates streptozotocin-induced diabetic nephropathy in rats: targeting TNF-α inflammatory pathway

Abstract

Objectives This study was designed to investigate the effect of Morus nigra fruit extract in retarding the progression of diabetic nephropathy in streptozotocin (STZ)-induced diabetic rats. Methods Diabetic male Wistar rats were injected with black mulberry fruit extract (BMFE) at doses of 150 and 300 mg/kg body weight. After 4 weeks, microalbuminuria was estimated in addition to serum concentrations of glucose, insulin, creatinine and albumin. Key findings The study revealed a significant amelioration of all the measured parameters in diabetic animals. In addition, MDA, lipid peroxide levels and catalase activity were also improved. The histopathological examination of kidney tissues revealed significant improvement of the pathological changes and glomerular sclerosis in diabetic rats treated with BMFE. Treated rats showed downregulation of TNF-α, vascular cell adhesion molecule-1 (VCAM-1) and fibronectin mRNA expression. Conclusion The ameliorative effect of BMFE on diabetic nephropathy is not only through its potent antioxidant and hypoglycaemic effects but also through its downregulation of TNF-α, VCAM-1 and fibronectin mRNA expression in renal tissues of diabetic-treated rats. Therefore, BMFE as dietary supplement could be a promising agent in improving diabetic nephropathy. Methods Chemicals Authentic anthocyanin samples of cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside for high-performance liquid chromatography (HPLC) analysis were purchased from Phytoplan company (Germany). Streptozotocin (STZ), chloroform and isopropanol were obtained from Sigma-Aldrich (St. Louis, MO, USA). Authentic samples for HPLC analysis of flavonoids rutin, quercetin, quercetrin, catechin, kaemferol, naringin and phenolic acids chlorogenic, gallic, caffeic, ellagic and cinnamic acids were purchased from Sigma-Aldrich, Germany and were kindly supplied by Food Technology Research Institute, Giza, Egypt. TRizol was obtained from Genetix Branid Co. (Genetix Biotech Asia Pvt. Ltd., New Delhi, India). QuantiFast SYBR Green PCR Master Mix unit was provided by QIAGEN (Hilden, Germany). HiSenScript TM [-] cDNA synthesis kit was purchased from iNtRON Biotechnology Company. The other reagents were of analytical, high-performance liquid chromatography (HPLC), or the best accessible pharmaceutical grades.

Vitamin D regulates insulin and ameliorates apoptosis and oxidative stress in pancreatic tissues of rats with streptozotocin-induced diabetes

“…Untreated DM can lead to numerous diseases and long-term complications, leading to death (Lotfy et al 2017). Recent evidence confirms that DM-induced chronic hyperglycemia can induce the formation of oxidative stress and free radicals in humans and animal models (Sadek et al 2017;Abouzed et al 2018;Alsenosy Abdel-wahab et al 2019;Abouzed et al 2020). Oxidative stress is the main factor that induces the secondary complications of DM, such as injuries and foot ulceration (Sivitz and Yorek 2010).…”

Antioxidative Stress and Anti-Inflammatory Activity of Fucoidan Nanoparticles against Nephropathy of Streptozotocin-Induced Diabetes in Rats

“…The administration of antioxidants fucoidan nanoparticles can improve kidney function by preventing oxidative tissue damage in diabetic nephropathy. The same result, the administration of exogenous antioxidants such as Syzygium aromaticum , Black mulberry fruit, and Heteroxenia ghardaqensis can inhibit ROS formation by scavenging the intracellular ROS that has been formed [ 17 , 18 , 28 ].…”

“…It was reported that streptozotocin can cause oxidative stress and inflammation, which can further damage the kidneys in diabetic rat model complications and eventually lead to nephropathy. Thus, agents that have antioxidant and anti-inflammation effects can be used to prevent nephropathy in diabetes [ 18 , 19 ]. It has been reported that fucoidan is a natural product that has a strong antioxidant effect.…”

Renoprotective impact of Dapagliflozin and Mulberry extracts toward Fr-STZ induced diabetic nephropathy in rats: Biochemical and Molecular aspects

“…Furthermore, Diabetic rats treated with mulberry fruit and leaves extract and mix showed an improvement in serum glucose, urea and creatinine levels. Similarly, Abouzed et al, [20] stated that the black mulberry fruit extract ameliorated the renal function biomarkers in diabetic rats. Mulberry extract might advantageously affect diabetic confusions, like renal dysfunction, by keeping up with blood glucose homeostasis in diabetic rats.…”

“…Group III (DAPA): diabetic rats received dapagli ozin (1 mg/Kg daily) by gavage as described by Oraby et al, [19] for four weeks following the rst two weeks of diabetes induction. Group IV (MFE): diabetic rats treated with mulberry fruit extract (300mg/kg b.wt) by gavage as described by Abouzed et al, [20] for six weeks. Group V (MLE): diabetic rats treated with mulberry leaves extract (250 mg/kg b.wt) by gavage as Hassanalilou et al, [15] for six weeks.…”